Vebreltinib Plus Chemotherapy as First-line Treatment for MET-overexpressing NSCLC

NCT07549061 | Not Yet Recruiting Phase 2

• 1 other identifier: PLB1001-GBD-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the efficacy and safety of vebreltinib plus platinum-doublet chemotherapy as first-line therapy in patients with driver gene-negative, locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET overexpression.

Conditions

Lung Neoplasms

Keywords

NSCLC; Vebreltinib; Met; Overexpression

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients whose tumor volume has reduced to a predetermined value and can maintain the minimum time limit.

  up to 24 months

Secondary Outcomes (4)

• PFS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

• DCR

  Each 42 days up to intolerance the toxicity or PD (up to 24 months

• OS

  From randomization until death (up to 24 months)

• AE

  From randomization until death (up to 24 months)

Study Arms (1)

vebreltinib+ platinum-based chemotherapy

EXPERIMENTAL

Drug: Vebreltinib; Drug: Chemotherapy

Interventions

Vebreltinib DRUG

vebreltinib，150mg，oral，bid

vebreltinib+ platinum-based chemotherapy

Chemotherapy DRUG

Administered in accordance with the approved label

vebreltinib+ platinum-based chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign a written informed consent form (ICF) to participate in the study; be willing and able to comply with study-related visits and procedures.
• Male or female subjects aged 18 years or older.
• Pathologically confirmed non-small cell lung cancer (NSCLC); outside hospital pathology reports are acceptable.
• Newly diagnosed metastatic NSCLC (clinical Stage IVA or IVB) or recurrent NSCLC (staged in accordance with the AJCC Cancer Staging Manual 9th edition), not eligible for curative-intent surgery or radiotherapy.
• Treatment-naïve advanced NSCLC not amenable to curative surgery or radiotherapy. For recurrent disease, prior adjuvant and neoadjuvant therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiotherapy/chemoradiotherapy with or without immunotherapy, biologic therapy, or investigational agents is permitted if completed at least 12 months before disease recurrence.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2.
• Driver gene-negative status confirmed by tumor tissue or blood sample, including but not limited to negative EGFR mutation, negative ALK rearrangement, negative ROS1 rearrangement, negative KRAS G12C mutation, and negative MET exon 14 skipping mutation. MET amplification is permitted: FISH demonstrating GCN ≥ 4 or MET/CEP7 ≥ 2, or positive result confirmed by NGS.
• MET protein overexpression defined as ≥50% of tumor cells staining at IHC 2++ or stronger. Local laboratory IHC results are acceptable.
• Estimated overall survival of at least 3 months.
• Laboratory values meeting the following requirements:
• Absolute neutrophil count (ANC)≥1.5 × 10⁹/L; Hemoglobin≥90 g/L; Platelets≥75 × 10⁹/L; Serum total bilirubin≤1.5×upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤3×ULN; for patients with liver metastases, AST and ALT≤5×ULN; Serum creatinine\<1.5 × ULN. Creatinine clearance (CrCl)\>50 mL/min, calculated using the Cockcroft-Gault formula
• Males with reproductive potential and females of childbearing potential must agree to use highly effective contraception from signing informed consent until 3 months after the last dose of study drug. For females of childbearing potential, a serum pregnancy test must be negative within ≤7 days before the first dose of study drug.

You may not qualify if:

• Spinal cord compression. Symptomatic or unstable brain metastases, unless the patient has completed curative treatment, is not receiving corticosteroid therapy, and has maintained a stable neurological status for at least 2 weeks after completion of curative treatment and steroid therapy. Patients with asymptomatic brain metastases may be included if the investigator determines there is no immediate indication for curative treatment.
• Meeting any of the following prior treatment history criteria:
• Major surgery (e.g., intrathoracic, intra-abdominal, or intrapelvic surgery) within 4 weeks prior to enrollment, or failure to recover from side effects of such surgery. Thoracoscopic biopsy and mediastinoscopy are not considered major surgery, and patients may be enrolled 1 week after these procedures.
• Treatment with traditional Chinese medicine (TCM) or Chinese patent medicine with anti-tumor indications within 1 week prior to the first dose of study drug.
• Treatment with strong CYP3A4 inducers and/or strong inhibitors, and inability to discontinue such agents for at least 1 week prior to initiation of study treatment and during the study period.
• Prior systemic anti-tumor therapy for advanced NSCLC, including chemotherapy, biologic therapy, immunotherapy, or any investigational agent, administered as non-curative surgery or radiotherapy. For recurrent disease, prior adjuvant and neoadjuvant therapy (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiotherapy/chemoradiotherapy with or without immunotherapy, biologic therapy, or investigational agents is permitted only if completed at least 12 months before disease recurrence.
• Radiation therapy to more than 30% of bone marrow, or large-field radiation therapy within 4 weeks prior to the first dose of vebreltinib.
• Any severe or uncontrolled systemic disease, including but not limited to other severe medical or psychiatric disorders or laboratory abnormalities that, in the investigator's judgment, render the study drug inappropriate for the patient or impair compliance with the protocol.
• Meeting any of the following cardiac function or disease criteria:
• Mean corrected QT interval (QTc) \> 470 ms based on three routine ECG assessments performed at least 5 minutes apart (preferably completed within 1 hour) during the screening period at rest. Calculation shall be performed using the Fridericia formula (see Appendix 5 for details), with mean QTcF \> 470 ms.
• Any significant cardiac arrhythmia, such as complete left bundle branch block, second- or third-degree heart block, ventricular arrhythmia, drug-uncontrolled supraventricular or nodal arrhythmia, or other drug-uncontrolled cardiac arrhythmias.
• Any risk factors for prolonged QTc interval, including chronic hypokalemia uncorrected by supplementation, congenital long QT syndrome, and concomitant use of QTc-prolonging medications.
• Congestive heart failure of New York Heart Association (NYHA) Class ≥3. Unstable or uncontrolled diseases or conditions related to or affecting cardiac function (e.g., unstable angina pectoris, inadequately controlled hypertension defined as diastolic blood pressure \> 100 mmHg and/or systolic blood pressure \> 160 mmHg regardless of antihypertensive use; initiation or adjustment of antihypertensive agents prior to screening is permitted).
• Diagnosis of another active malignancy requiring treatment within the past 3 years, other than NSCLC. Excluded are completely resected basal cell and squamous cell skin cancer, and completely resected carcinoma in situ of any type.
• Presence of active infection, including but not limited to:

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

241 West Huaihai Road, Xuhui District, Shanghai, 200030, China.

Shanghai, Shanghai Municipality, China

Location

Related Publications (4)

• Tsao MS, Sholl L, Shiller M, Illei P, Wistuba II, Beasley MB, Schalper KA, Simmons A, Ansell P, Beruti S, Mino-Kenudson M. MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer. NPJ Precis Oncol. 2025 Nov 20;9(1):369. doi: 10.1038/s41698-025-01144-9.

  PMID: 41266553 RESULT

• Camidge DR, Bar J, Horinouchi H, Goldman J, Moiseenko F, Filippova E, Cicin I, Ciuleanu T, Daaboul N, Liu C, Bradbury P, Moskovitz M, Katgi N, Tomasini P, Zer A, Girard N, Cuppens K, Han JY, Wu SY, Baijal S, Mansfield AS, Kuo CH, Nishino K, Lee SH, Planchard D, Baik C, Li M, Ansell P, Xia S, Bolotin E, Looman J, Ratajczak C, Lu S. Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial. J Clin Oncol. 2024 Sep 1;42(25):3000-3011. doi: 10.1200/JCO.24.00720. Epub 2024 Jun 6.

  PMID: 38843488 RESULT

• Hass R, Jennek S, Yang Y, Friedrich K. c-Met expression and activity in urogenital cancers - novel aspects of signal transduction and medical implications. Cell Commun Signal. 2017 Feb 17;15(1):10. doi: 10.1186/s12964-017-0165-2.

  PMID: 28212658 RESULT

• Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.

  PMID: 39036382 RESULT

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Wei Nie

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Nie

CONTACT

021-63846590; niewei-1001@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shanghai Chest Hospital

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 23, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)